Mitochondrial aspartate aminotransferase: a third kynurenate‐producing enzyme in the mammalian brain
@article{Guidetti2007MitochondrialAA, title={Mitochondrial aspartate aminotransferase: a third kynurenate‐producing enzyme in the mammalian brain}, author={Paolo Guidetti and Laura Amori and Michael T. Sapko and Etsuo Okuno and Robert M. Schwarcz}, journal={Journal of Neurochemistry}, year={2007}, volume={102} }
The tryptophan metabolite kynurenic acid (KYNA), which is produced enzymatically by the irreversible transamination of l‐kynurenine, is an antagonist of α7 nicotinic and NMDA receptors and may thus modulate cholinergic and glutamatergic neurotransmission. Two kynurenine aminotransferases (KAT I and II) are currently considered the major biosynthetic enzymes of KYNA in the brain. In this study, we report the existence of a third enzyme displaying KAT activity in the mammalian brain. The novel…
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Structure, expression, and function of kynurenine aminotransferases in human and rodent brains
- Biology, ChemistryCellular and Molecular Life Sciences
- 2009
The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.
Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II.
- Biology, ChemistryBioscience reports
- 2008
Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested alpha-oxo acids as amino-group acceptors.
Thermal stability, pH dependence and inhibition of four murine kynurenine aminotransferases
- Biology, ChemistryBMC Biochemistry
- 2010
The characteristics reported here could be used to develop specific assay methods for each of the four murine KATs and identify which KAT is affected in mouse models for research and to develop small molecule drugs for prevention and treatment of KAT-involved human diseases.
Human kynurenine aminotransferase II – reactivity with substrates and inhibitors
- Biology, ChemistryThe FEBS journal
- 2011
Spectroscopic and functional characterization of both the human wild‐type KATII and a variant carrying the active site mutation Tyr142→Phe and the availability of these assays and spectroscopic analyses demonstrated that (R)‐2‐amino‐ 4‐(4‐(ethylsulfonyl))‐4‐oxobutanoic acid and cysteine sulfinate, reported to be K ATII inhibitors, are poor substrates that undergo slow transamination.
Inhibition of human kynurenine aminotransferase isozymes by estrogen and its derivatives
- Biology, ChemistryScientific Reports
- 2017
Inhibition assay results and modelling suggests that the 17-sulfate moiety in estradiol disulfate is very important in improving its potency as an inhibitor, increasing the inhibition by approximately 10–100 fold compared to Estradiol.
Biochemical and Structural Properties of Mouse Kynurenine Aminotransferase III
- Biology, ChemistryMolecular and Cellular Biology
- 2008
It is established that mKAT III is able to efficiently catalyze the transamination of kynurenine to KYNA and has optimum activity at relatively basic conditions of around pH 9.0 and at relatively high temperatures of 50 to 60°C.
Alternative kynurenic acid synthesis routes studied in the rat cerebellum
- Biology, ChemistryFront. Cell. Neurosci.
- 2015
Results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative routes forKYNA production.
Kynurenic acid and 3-hydroxykynurenine production from d-kynurenine in mice
- Biology, ChemistryBrain Research
- 2012
Crystal Structure of Human Kynurenine Aminotransferase II*
- Biology, ChemistryJournal of Biological Chemistry
- 2008
The protein architecture of hKAT-II reveals that it belongs to the fold-type I pyridoxal 5-phosphate (PLP)-dependent enzymes, and it is proposed that hKat-II represents a novel subclass in the Fold- type I enzymes because of the unique folding of its first 65 N-terminal residues.
Pharmacological Manipulation of Kynurenic Acid
- Biology, PsychologyCNS drugs
- 2009
Low endogenous levels of rat brain KYNA have been found to reduce firing of midbrain dopamine neurons, and mice with a targeted deletion of kynurenine aminotransferase II display low endogenous brainKYNA levels concomitant with an increased performance in cognitive tests.
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